1

INTRAVENOUS PARACETAMOL USE

Addendum to the 2008 ‘Paracetamol Use’ Position Statement

of the NSW Therapeutic Advisory Group Inc. [1]

20 December 2012

This document has been prepared in response to recent changes to the Product Information for

intravenous (IV) paracetamol (Perfalgan®) and aims to provide guidance on the appropriate and safe

use of IV paracetamol in paediatric and adult patients. It is presented in two sections:

Paediatric issues: Background & recommendations

Adult issues: Background & recommendations

These recommendations have been developed by the NSW Therapeutic Advisory Group (TAG)

Editorial Committee, following its usual processes [2]. This has included review of published

research evidence; unpublished data (e.g. from drug regulatory bodies and pharmaceutical industry

sources); review of up-to-date paediatric prescribing information sources (e.g., BNF for Children

and other published guidelines); and input from a multi-disciplinary group of health professionals

with paediatric and adult expertise in clinical pharmacology and therapeutics, toxicology, health

technology assessment and medicines evaluation, clinical pharmacy, clinical medicine and nursing.

(See acknowledgements for details.)

This addendum should be read in conjunction with:

(a) NSW TAG’s 2008 “Paracetamol Use” position statement [1], which is cross referenced in

relevant places as indicated

http://www.ciap.health.nsw.gov.au/nswtag/documents/publications/position-

statements/paracetamol-use-dec-2008.pdf

(b) NSW Health’s Policy Directive PD2009_009 Paracetamol Use.

http://www0.health.nsw.gov.au/policies/pd/2009/PD2009_009.html This work is copyright of the NSW Therapeutic Advisory Group Inc. Apart from any use as permitted under the Copyright Act 1968, no part of this information may be reproduced by any process without written permission. Whilst the information contained in this document has been presented with all due care, and the information is considered to be true and correct at the date of publication, changes in circumstances after publication may impact on the accuracy of the information. This document represents expert consensus opinion and should not be relied on as professional advice other than in this context. The information provided should not be regarded as a substitute for detailed expert advice in individual cases. NSW Therapeutic Advisory Group Inc will accept no responsibility for any loss, claim or damage suffered or caused by any person acting or refraining from action as a result of any material in this document.

An initiative of NSW clinical pharmacologists

and pharmacists funded by the NSW Ministry

of Health.

2

1.1 BACKGROUND TO PAEDIATRIC ISSUES

In September 2009, changes were made to the approved Australian product information for intravenous

(IV) paracetamol [Perfalgan®], halving the recommended dose in term neonates, infants, toddlers and

children weighing less than 10 kg, from 15 mg/kg/dose to 7.5 mg/kg/dose (not exceeding 4

administrations per day).[3] This lower dose had been the registered dose in the UK and the rest of

Europe since the product was first licensed there in 2001/2002.

NSW Therapeutic Advisory Group (TAG)’s communication with the Therapeutic Goods Administration

(TGA) indicated that the sponsor, Bristol Myer Squibb Australia Pty Ltd (BMS), requested the dose

reduction in the context of toxicity occurring in vulnerable populations.[4] These changes were initiated

by BMS’s UK counterpart due to safety concerns and not on the basis of new pharmacokinetic data.[5]

The majority of reported cases of toxicity and safety concerns in infants < 10 kg have been due to

administration of inadvertent 10-fold overdoses of IV paracetamol.[6] In 2010, the UK Medicines

Healthcare Products Regulatory Agency (MHRA) noted that 23 cases of IV paracetamol overdose had

been reported in infants < 1 year worldwide, one of which was fatal; 19 of these cases occurred in the

European Union, including 7 in the UK in which a 10-fold error was generally reported.[6] By the end of

October 2010 over 200 cases of inadvertent overdose of IV paracetamol had been reported to the National

Reporting and Learning System (NRLS) of the UK’s National Health Service.[7] There have also been

multiple recent literature reports of 10-fold overdoses with IV paracetamol in young infants.[8–11]

There have been no reports of toxicity with IV paracetamol administered at therapeutic doses in

low risk infants in recent published literature [12], or any reports to the TGA since the introduction of IV

paracetamol in Australia.[13]

The strength of Perfalgan® (10 mg/mL) and the existence of two different vial sizes (1000 mg/100 mL

and 500 mg/50 mL) are identified as major contributing factors to reported paediatric medication errors

with the intravenous formulation, especially 10-fold dosing errors.[9,14] Many of the accidental

overdoses appear to be related to confusion between mg and mL doses; for example, the dose would be

calculated in mg (150 mg) and the IV Perfalgan® administered in the same number of mL (150 mL

instead of 15 mL of the 10 mg/mL solution) resulting in a 10-fold overdose.

A generic product, Paramat®, has been approved for marketing in Australia.[15] The newer generic

product Paramat®, paracetamol 1000 mg/100 mL injection solution, from Actavis Pty Ltd is only

available in a 100 mL vial size.

Other contributing factors in reported cases of inadvertent overdose include concomitant administration

of oral paracetamol (including that in combination products such as Panadeine® and Panadeine Forte

®),

calculation errors including dose calculation error due to incorrect weight, and non-adherence to

recommended doses.[16–17]

3

1.2 RECOMMENDATIONS FOR PAEDIATRICS

1.2.1 General

IV paracetamol should be considered a high risk medicine when administered to infants

and young children.

IV paracetamol should only be used for acute, short-term treatment of mild to moderate

pain when oral or rectal dosing is not possible.[1: page 10]

IV paracetamol should be replaced by enteral paracetamol at the earliest opportunity

[1: page 10]; oral administration is preferred since rectal absorption can be delayed or

erratic.[1: page 12]

Use of paracetamol should always be preceded by a comprehensive risk assessment and

reviewed every 24 hours. This includes particular caution in considering paracetamol use in

infants < 6 months.

General principles for safe paediatric prescribing and safe paracetamol prescribing apply.[18–

19]

1.2.2 Dose

Although the TGA approved dose for infants < 10 kg is now 7.5 mg/kg/dose 4–6 hourly (max

30 mg/kg/day), pharmacokinetic data [20–21] and recent published clinical evidence [22]

support the use of 15 mg/kg/dose (max 60 mg/kg/day).

The 2011–2012 edition of the British National Formulary for Children has recommended

increasing the dose of IV paracetamol for infants, from 7.5 mg/kg/dose to 15 mg/kg/dose

every 4–6 hours.[23] This change was agreed by their expert advisers and Paediatric

Formulary Committee in November 2010.[24]

In view of the above, and the lack of any evidence of toxicity occurring in low risk infants

receiving recommended doses of IV paracetamol, NSW TAG does not recommend any

changes to the original dose recommendations for infants contained in its 2008 position

statement.

Risk factors for hepatotoxicity include:

febrile illness

younger age

prolonged fasting

vomiting or dehydration

chronic undernutrition

severe hepatic impairment [18] [1: pages 7–10]

The recommended dose of IV paracetamol for infants >3 months

of age remains 15 mg/kg/dose every 6 hours up to a maximum

of 60 mg/kg/day (never exceeding 1 g per dose and 4 g in 24

hours).[1: page 11]

4

This dose of paracetamol is now “off-label” but falls within the category of “routine off-label

use justified”, and meets appropriateness criteria as specified in the NSW Health Policy

Directive PD2008_037 on Evaluation of Medicines for Use in Public Hospitals.[25]

1.2.3 Additional safety measures to prevent accidental overdoses

When prescribing or administering IV paracetamol, clinicians should first check that no

other formulations of paracetamol are concurrently prescribed or administered, and that

the safe maximum daily dose of paracetamol (from all sources including combination

products such as Panadeine® and Panadeine Forte

®) is not exceeded.

In the “drug name” section of the medication chart the prescriber should write “Paracetamol

IV” and should additionally specify the brand name in brackets after this, e.g., (“Perfalgan”)

or (“Paramat”) to avoid confusion with other paracetamol formulations.

The dose should be calculated using the patient’s current, accurate weight and

independently double-checked at the time of prescribing AND at each administration. (Use

of a calculator is highly recommended.)

The dose should be prescribed in milligrams (mg) AND millilitres (mL) to maximise the

clarity of the intended dose: for example, for a 10 kg infant, “150 mg Paracetamol IV (15 mL

Perfalgan or Paramat)”. When specifying the dose in mL, it is important to clearly indicate

the IV route in the order to avoid confusion with oral liquid formulations.

Paracetamol orders should only have one route specified (i.e., orders should NOT be written

as IV/PO/PR as this is not appropriate and is unsafe).

The IV paracetamol vial should not be hung as an infusion in neonates, infants and children

weighing less than 33 kg. The volume containing the required dose should be drawn up

with a syringe (for infants weighing < 10 kg use a 5 mL or 10 mL syringe), diluted in 0.9%

sodium chloride or 5% glucose solution and administered as an infusion.[16]

Dosing for overweight or obese children should be based on ideal body weight

not total body weight.[1: page 13; 18,26]

For obese children, calculation of paracetamol dose using actual bodyweight

may lead to a relative overdose. The ‘ideal weight’ for dose calculation

purposes for a child may be approximated using growth charts which are

widely available in health care facilities or, if local charts are not available,

alternatives can be accessed at http://www.cdc.gov/growthcharts/

If age and height are known, a height growth chart will indicate the

percentile at which to read the weight from a weight growth chart.

If only age is known, reading from the 50th percentile on a weight

growth chart is a practical and expedient method for weight estimation.

5

Clinicians should take special precautions to ensure that oral paracetamol liquid is not

administered by the IV route inadvertently. Special oral dispensers should be used for oral

paracetamol administration.[27]

In cases where an accidental overdose of IV paracetamol has been administered, a toxicologist

should be consulted for appropriate management advice. The most recent Australian guidelines

for the management of paracetamol overdoses now provide an updated treatment nomogram,

recommended investigations and N-acetylcysteine dosing regimens.[28]

1.2.4 System issues and implementation

Hospitals are strongly encouraged to evaluate how current practices align with these

recommendations and to initiate appropriate educational and other strategies to address any

areas of suboptimal practice identified.

Use of an effective, evidence-based implementation model [19] is recommended.

Hospitals are encouraged to consider limiting IV paracetamol prescribing and availability to

specified prescribers and wards.

All such prescribers and nursing staff should be appropriately educated in safe

paediatric prescribing principles and in the appropriate and safe use of IV

paracetamol in children. See references 18−19 for available educational resources for

safe paediatric prescribing.

6

2.1 BACKGROUND TO ADULT ISSUES

2.1.1 Dose for underweight adults or frail older people less than 50 kg

The product information for Perfalgan®

was further updated in April 2012 to describe dosing in small

adults [3]:

For patients weighing 50 kg or more, the total daily dose of paracetamol should not exceed 4 g

For patients weighing ≤ 50 kg and > 33 kg, the dose is 60 mg/kg/day (not exceeding 3 g)

For patients weighing ≤ 33 kg and > 10 kg, the dose is 60 mg/kg/day (not exceeding 2 g)

These weight adjusted doses are based on pharmacokinetic principles since there is a lack of data on

efficacy or safety from studies in smaller adults. Mitchell et al did not observe any hepatotoxicity in

robust or frail inpatients ≥ 70 years given a maximum of 3 g or 4 g paracetamol per day; weight was not a

specific consideration.[29] There are animal data to suggest old age may be protective against

paracetamol hepatotoxicity although it may increase susceptibility to nephrotoxicity.[30] The maximum

doses are conservative especially for adults with an ideal body weight at the upper end of the weight

categories.

2.1.2 Use in stroke

In the 2008 NSW TAG Position Statement, paracetamol was recommended for use in acute pain and

symptomatic fever > 38.5 °C.[1] In patients with acute stroke, increased body temperature can be

centrally driven or a result of concurrent infection, and is associated with poorer clinical outcomes.[31,32]

Administration of paracetamol for temperature reduction when body temperature is > 37.5 °C has become

standard of care in many settings.[32−34] National and international stroke guidelines give mixed advice,

with Australia and Canada recommending investigation of increasing body temperature and use of

antipyretic medications, the UK allowing their use and the US and Europe finding the evidence for

effectiveness of antipyretic use inconclusive but acknowledging the practice.[32,35–38]

Small trials have investigated the use of paracetamol for temperature reduction in stroke patients and

shown modest effect.[39–43] Dippel et al have shown that, compared to placebo, paracetamol 1000 mg

given 6 times daily reduced the body temperature of acute stroke patients by an average of 0.26 °C within

4 hours of the first dose and the effect lasted for the remaining treatment period of 20 hours.[44] Sulter

deemed acetaminophen (1000 mg 4 hourly per rectum) "insufficient for reducing an elevated body

temperature to a state of normothermia”.[42]

In a large randomised controlled clinical trial [n=1696] Middleton et al showed a 15.7% difference in

mortality or functional dependency at 90 days, irrespective of stroke severity, when acute stroke patients

were given a 'bundled' intervention to manage fever (defined as temperature ≥ 37.5 °C), hyperglycaemia

and swallowing dysfunction for the first 72 hours after admission.[33] This included 4 hourly temperature

measurements and treatment of temperatures of 37.5 °C or over with intravenous, rectal or oral

paracetamol.

7

The PAIS-2 trial is underway to determine if temperature reduction with paracetamol has an effect on

neurological outcome after stroke [45] but at this stage there is no clearly established evidence for the

clinical benefits of temperature reduction alone.[38,46] Furthermore, it is worth noting that prophylactic

temperature reduction may potentially mask signs of an underlying infection.[46]

8

2.2 RECOMMENDATIONS FOR ADULTS

2.2.1 General

Paracetamol orders should only have one route specified (i.e., orders should NOT be written as

IV/PO/PR as this is not appropriate and is unsafe).

IV paracetamol should be replaced by enteral paracetamol at the earliest opportunity [1: page 10];

oral administration is preferred since rectal absorption can be delayed or erratic.[1: page 12]

When prescribing or administering IV paracetamol, clinicians should first check that no other

formulations of paracetamol are concurrently prescribed or administered, and that the safe

maximum daily dose of paracetamol (from all sources including combination products such as

Panadeine® and Panadeine Forte

®) is not exceeded.

In the “drug name” section of the medication chart the prescriber should write “Paracetamol IV”

and should additionally specify the brand name in brackets after this, e.g., (“Perfalgan”) or

(“Paramat”) to avoid confusion with other paracetamol formulations.

2.2.2 Dose for underweight adults or frail older people less than 50 kg

NSW TAG does not recommend any changes to the original dose recommendations

contained in its 2008 position statement i.e., 15 mg/kg/dose every 4−6 hours up to four

times daily (60 mg/kg/day) for frail, older patients and adults < 50 kg.[1: page 10]

Dosing should be based on actual body weight.

Risk factors for hepatotoxicity that need to be considered for these patients include:

prolonged fasting [1: pages 8]

reduced intake that might occur prior to hospital admission for an acute

illness [1: pages 8]

severe hepatic impairment [1: pages 8]

In patients with chronic or compensated active hepatic disease, the

maximum daily dose should not exceed 3 g/day

The product information notes that hepatic failure or

decompensated active liver disease should be regarded as a

contraindication to paracetamol use. (The degree of hepatic failure

that is of concern has not been defined in the product information)

9

If still receiving IV paracetamol at 48 hours and, if after clinical review, a decision to

continue IV paracetamol is made then monitoring of liver enzymes (ALT, AST) and

International Normalised Ratio (INR), is recommended. [1: page 13]

2.2.3 Use in stroke

NSW TAG recognises that paracetamol is used for temperatures ≥ 37.5 °C in otherwise

asymptomatic patients with acute stroke.[33] This practice appears to be based on limited

evidence of benefit (in terms of impact on stroke outcomes) and may need to be reviewed as

additional evidence becomes available.

Patients who develop a fever should have appropriate clinical evaluation to promptly assess

and treat any concurrent infection.[32]

NSW TAG notes that the NSW Agency for Clinical Innovation (ACI) is currently developing

comprehensive guidance for stroke management. Practitioners are encouraged to refer to this

when available.

2.2.4 System issues and implementation

Hospitals are strongly encouraged to evaluate how current practices align with these

recommendations and to initiate appropriate educational and other strategies to address any

areas of suboptimal practice identified.

Use of an effective, evidence-based implementation model [19] is recommended.

Hospitals are encouraged to consider limiting IV paracetamol prescribing and availability to

specified prescribers and wards.

All such prescribers and nursing staff should be appropriately educated in the

appropriate and safe use of IV paracetamol.

10

REFERENCES

[1] NSW Therapeutic Advisory Group. Paracetamol Use: A Position Statement of the NSW Therapeutic Advisory Group Inc.,

December 2008 [Available at: http://www.ciap.health.nsw.gov.au/nswtag/reviews/position-statements.html ]

[2] Editorial Committee, NSW Therapeutic Advisory Group. Development process for NSW TAG guidance documents,

December 2007 [Available at: http://www.ciap.health.nsw.gov.au/nswtag/reviews/about-reviews.html ]

[3] Approved Product Information: Perfalgan® Solution for infusion. Bristol Myers Squibb Australia Pty Ltd, April 2012

[4] Personal communications: Dr Kerri Mackay (Delegate of the Secretary), Department of Health and Ageing, Therapeutic

Goods Administration, 12 May 2010 and Dr Ruth Lopert (Principal Medical Advisor), Department of Health and Ageing,

Therapeutic Goods Administration, 21 January 2011

[5] Personal communications: Gabrielle Formosa (Medical Information Associate), Bristol-Myers Squibb Australia Pty Ltd, 14

April 2010 and Joanne Skinner (Medical Information Associate), Bristol-Myers Squibb Australia Pty Ltd, 28 May 2012

[6] MHRA. Intravenous paracetamol (Perfalgan▼): risk of accidental overdose, especially in infants and neonates. Drug Safety

Update 2010; 3 (12): 2

[7] NHS. Patient safety resources: Overdose of intravenous paracetamol in infants and children | Signal 1923. NHS Direct, 29

October 2010 [Accessed at http://www.nrls.npsa.nhs.uk/resources/?EntryId45=83757 on 5 August 2012]

[8] Berling I, Anscombe M, Isbister GK. Intravenous paracetamol toxicity in a malnourished child. Clin Toxicol 2012; 50: 74-76

[9] Dart RC, Rumack BH. Intravenous Acetaminophen in the United States: Iatrogenic Dosing Errors. Pediatrics 2012; 129(2):

349-353

[10] Beringer RM, Thompson JP, Parry S, Stoddart PA. Intravenous paracetamol overdose: two case reports and a change to

national treatment guidelines. Arch Dis Child 2011; 96: 307-308

[11] Nevin DG, Shung J. Intravenous paracetamol overdose in a preterm infant during anesthesia [letter]. Ped Anesthesia 2009;

20: 105-107

[12] Lavonas EJ, Reymolds KM, Dart RC. Therapeutic acetaminophen is not associated with liver injury in children: a systematic

review. Pediatrics 2010; 126 (6): e1430-44

[13] Personal communication: Dr Bronwen Harvey, Senior Medical Officer and Delegate of the Secretary, Department of Health

and Ageing, Therapeutic Goods Administration, 21 August 2012

[14] Cavell GF. A safer presentation of intravenous paracetamol is needed [letter]. Eur J Hosp Pharm 2012; 0 (0): 1

[15] Approved Product Information: Paramat® Solution for Infusion. Actavis Australia Pty Ltd, 20 June 2011

[16] Dear Healthcare Professional Letter. Bristol-Myers Squibb Australia Pty Ltd. May, 2012

[17] Australian Government, Department of Health and Ageing, Therapeutic Goods Administration. Medicines Safety Update:

Accidental paracetamol poisoning. Aust Prescriber 2012; 35(4): 122

[18] Gazarian M, Graudins LV. “Safe Prescribing” and “Paracetamol” guidelines. In: Supplemental Information (SI 1-10). Long-

term Reduction in Adverse Drug Events: An Evidence-based Improvement Model. Pediatrics 2012; 129: e1334.

[19] Gazarian M, Graudins LV. Long-term Reduction in Adverse Drug Events: An Evidence-based Improvement Model.

Pediatrics 2012; 129: e1334-1342

[20] Autret E, Dutertre J-P, Breteau M et al. Pharmacokinetics of Paracetamol in the Neonate and Infant after Administration of

Propacetamol Chlorohydrate. Dev Pharmacol Ther 1993; 20: 129-134

[21] Allergaert K, Anderson BJ, Naulaers G et al. Intravenous paracetamol (propacetamol) pharmacokinetics in term and preterm

neonates. Eur J Clin Pharmacol 2004; 60: 191-197

[22] Wilson-Smith EM, Morton NS. Survey of i.v. paracetamol (acetaminophen) use in neonates and infants under 1 year of age

by UK anesthetists. Paediatr Anaesth 2009; 19(4): 329-37

11

[23] Paediatric Formulary Committee. BNF for Children [online]. London: BMJ Group, Pharmaceutical Press, and RCPCH

Publications. [Accessed via http://www.ciap.health.nsw.gov.au/home.html on 8 May 2012]

[24] Personal communication: Manjula Halai (Clinical Writer), Pharmaceutical Press, 9 May 2012

[25] NSW Health. Policy Directive PD2008_037 Medicine – Evaluation of Medicines for Use in Public Hospitals, July 2008.

[Available at: http://www.health.nsw.gov.au/policies/pd/2008/PD2008_037.html ]

[26] Wiese MD, Sluggett JK, Wilson CJ et al. Perceived and actual paracetamol dosing in overweight and obese children. Eur J

Hosp Pharm 2012; 0: 1-5. doi:10.1136/ejhpharm-2011-000031

[27] Medicines Advisory Group. Paracetamol Guideline. Sydney Children’s Hospital, Randwick, August 2011

[28] Daly FF, Fountain JS, Murray L, Graudins A, Buckley NA. Guidelines for the management of paracetamol poisoning in

Australia and New Zealand – explanation and elaboration. A consensus statement from clinical toxicologists consulting to the

Australian poisons information centres. Med J Aust 2008; 188(5): 296-301

[29] Mitchell SJ, Hilmer SN, Murnion BP and Matthews S. Hepatotoxicity of therapeutic short-course paracetamol in hospital

inpatients: impact of ageing and frailty. J Clin Pharm Ther 2011; 36: 327–335

[30] Rikans LE, Moore DR. Acetaminophen Hepatotoxicity in Aging Rats. Drug Chem Toxicol 1988; 11 (3): 237- 247

[31] Greer DM, Funk SM, Reaven NL et al. Impact of Fever on Outcome in Patients With Stroke and Neurologic Injury: A

Comprehensive Metanalysis. Stroke 2008; 39; 3029-3035

[32] The European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Guidelines for the

Management for Ischaemic Stroke and Transient Ischaemic Attack 2008. Cerebrovasc Dis 2008; 25: 457-507

[33] Middleton S, McElduff P, Ward J et al. Implementation of evidence-based treatment protocols to manage fever,

hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial. Lancet 2011; 378

(9804): 1699-1706

[34] Kallmunzer, B. Beck, A. Schwab, S. Kollmar, R. Antipyretic strategies for acute stroke: a nationwide survey among German

stroke units [abstract]. Nervenarzt 2010; 81 (6): 734-9

[35] National Stroke Foundation. Clinical Guidelines for Stroke Management 2010: Melbourne, Australia

[36] The Canadian Stroke Strategy. Canadian Best Practice Recommendations for Stroke Care: Summary (Updated 2008). CMAJ

2008; 179(12 Suppl): S1-S25

[37] Scottish Intercollegiate Guidelines Network (SIGN). Management of patients with stroke of TIA: assessment, investigation,

immediate management and secondary prevention. A national clinical guideline (108). NHS Quality Improvement Scotland,

December 2008

[38] Adams HP, del Zoppo G, Alberts, Mark J et al. Guidelines for the early management of adults with ischemic stroke: a

guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council,

Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care

Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this

guideline as an educational tool for neurologists. Circulation 2007; 115(20): e478-e534

[39] Dippel DW, van Breda EJ, van der Worp HB et al. Effect of paracetamol (acetaminophen) and ibuprofen on body

temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690].

BMC Cardiovascular Disorders 2003; 3: 2

[40] Dippel DW, van Breda EJ, van Gemert HM et al. Effect of paracetamol (acetaminophen) on body temperature in acute

ischemic stroke: a double-blind, randomized phase II clinical trial. Stroke 2001; 32(7): 1607-12

[41] Kasner SE, Wein T, Piriyawat P et al. Acetaminophen for altering body temperature in acute stroke: a randomized clinical

trial. Stroke 2002; 33(1): 130-4

[42] Sulter G, Elting JW, Maurits N et al. Acetylsalicylic acid and acetaminophen to combat elevated body temperature in acute

ischemic stroke. Cerebrovascular Diseases 2004; 17(2-3): 118-22

12

[43] Den Hertog HM, van der Worp HB, van Gemert HMA et al. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a

multicentre, randomised, placebo-controlled, phase III trial. Lancet Neurology 2009; 8(5): 434-440

[44] Dippel DWJ, van Breda EJ, van der Worp HB et al. Timing of the effect of acetaminophen on body temperature in patients

with acute ischemic stroke. Neurology 2003; 61: 677-679

[45] de Ridder I,. van der Worp HB, van Gemert HM et al. Does paracetamol improve recovery after stroke? [abstract]

Nederlands Tijdschrift voor Geneeskunde 2011; 155(46): A4169

[46] Den Hertog HM, van der Worp HB, Tseng MC, Dippel DJW. Cooling therapy for acute stroke (Review). The Cochrane

Library 2009; Issue 1

13

ACKNOWLEDGEMENTS

This document has been prepared by:

Ms Anna Drew

Quality Use of Medicines (QUM) Project Officer (and pharmacist), NSW Therapeutic

Advisory Group

Associate Professor Madlen Gazarian

Consultant in Paediatric Clinical Pharmacology & Therapeutics, Pharmacoepidemiology

and Pharmacovigilance; Honorary Associate Professor, Faculty of Medicine, University

of NSW

On behalf of the NSW Therapeutic Advisory Group (TAG) Editorial Committee, with guidance in

consultation with an Expert Advisory Group:

Dr Sasha Bennett

Executive Officer (and pharmacist), NSW Therapeutic Advisory Group

Associate Professor Madlen Gazarian

Consultant in Paediatric Clinical Pharmacology and Therapeutics,

Pharmacoepidemiology and Pharmacovigilance; Honorary Associate Professor, Faculty

of Medicine, University of NSW

Professor Garry Graham

Honorary Visiting Professor, University of New South Wales; St Vincent’s Hospital Sydney

Professor Andrew McLachlan

Professor of Pharmacy (Aged Care), Faculty of Pharmacy, University of Sydney; Centre

for Education and Research on Ageing, Concord Hospital

Professor J Paul Seale

Professor of Clinical Pharmacology, Sydney University Medical School

Professor Ian Whyte

Head, Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle

With contributions from:

NSW TAG SAFER Medicines Group

NSW TAG also gratefully acknowledges contribution from the following individuals:

Dr Michael Amos

Anaesthetist, Concord Repatriation Hospital, Sydney Local Health District; Co-Chair of

the ACI Anaesthesia Preoperative Care Clinical Network

Professor Craig Anderson

14

Senior Director, Neurological & Mental Health Division and Professor of Stroke

Medicine and Clinical Neuroscience, University of Sydney; Head, Department of

Neurology, Royal Prince Alfred Hospital

Ms Julie Arena

Senior Pharmacist, Sydney Children’s Hospitals Network (Randwick)

Mr Peter Barclay

Director of Pharmacy, Sydney Children’s Hospitals Network (Westmead)

Associate Professor John Collins AM

Head of Department, Pain Medicine and Palliative Care, Sydney Children’s Hospitals

Network (Westmead)

Ms Simeon Dale

Nursing Research Institute, St Vincent’s and Mater Health Sydney; National Centre for

Clinical Outcomes Research and School of Nursing, Midwifery and Paramedicine,

Australian Catholic University

Dr Jonathan De Lima

Staff Specialist, Paediatric Anaesthesiology, Sydney Children’s Hospitals Network

(Westmead)

Ms Paula Doherty

Quality Use of Medicines Pharmacist, John Hunter Hospital

Yasna Goodwin and members of the ADR report team (acting for Dr Bronwyn Harvey,

Senior Medical Officer and Delegate of the Secretary to the Department of Health and

Ageing)

Office of Product Review, TGA

Associate Professor Sarah Hilmer

Department of Clinical Pharmacology & Geriatric Medicine, Royal North Shore

Hospital; University of Sydney

Ms Katie Kerr

Medication Safety Project Officer (and pharmacist), NSW Therapeutic Advisory Group

Mr Daniel Lalor

Project Manager, Medication Safety, Clinical Excellence Commission

Dr Jocelyn Lowinger

Quality Use of Medicines and Publication Officer (and medical practitioner), NSW

Therapeutic Advisory Group (to May 2011)

Ms Judith Mackson,

Chief Pharmacist, Pharmaceutical Services Unit, Legal and Regulatory Services Branch,

NSW Ministry of Health

Professor Ross MacPherson,

Senior Staff Specialist, Department of Anaesthesia and Pain Management, Royal North

Shore Hospital

15

Professor Sandy Middleton

Nursing Research Institute, St Vincent’s and Mater Health Sydney; National Centre for

Clinical Outcomes Research and School of Nursing, Midwifery and Paramedicine,

Australian Catholic University

Ms Felicity Prior

Director (and pharmacist), Hunter Drug Information Service, Calvary Mater Newcastle

Ms Gillian Sharratt

Executive Officer (and pharmacist), NSW Therapeutic Advisory Group (to Jan 2012)

Ms Leone Snowden

Manager (and pharmacist), NSW Medicines Information Centre

Professor Les White

Chief Paediatrician, NSW Ministry of Health